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Adverse Events Reported Among Pediatric Patients Treated With JAK Inhibitors
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- This review highlights data regarding adverse events associated with the use of commercially available JAK inhibitors, including infections, constitutional symptoms, and increased risks of respiratory, cardiac, vascular, and renal disorders. In pediatric patients, acne was the most common adverse event. Children had a higher risk of developing blood and lymphatic disorders, whereas adults had a higher risk of developing nervous system and musculoskeletal/connective tissue disorders.
- The data from this review may aid in counseling patients and their caregivers before starting therapy and guiding treatment monitoring after therapy initiation.
abstract
This abstract is available on the publisher's site.
Access this abstract nowJanus kinase inhibitors (JAKi) are drugs that block tyrosine kinases responsible for transducing cytokine signals. The first JAKi was approved by the US Food and Drug Administration (FDA) in 2011 to treat rheumatoid arthritis in adults. A pediatric indication was not approved until 8 years later, for acute graft-versus-host disease. Since then, topical and oral formulations have gained FDA approval for pediatric patients with dermatologic diseases. While increasing evidence supports the safety of these medications in adults, data are limited in children. We sought to determine whether JAKi adverse events (AEs) as reported in clinical trials and via postapproval pharmacovigilance services are comparable in adult and pediatric patients. Pharmacovigilance data were extracted from the FDA's Adverse Event Reporting System and the Canada Vigilance Adverse Reaction Online Database for baricitinib, upadacitinib, abrocitinib, ruxolitinib, and tofacitinib. The pooled data were analyzed to detect the most common AEs for specific JAKi and for the drug class. We assessed 399,649 AEs from 133,216 adults and 2883 AEs from 955 patients under 18 years old and identified slightly different AE profiles for the two age groups. Both populations had increased risk for infections and gastrointestinal AEs. However, pediatric patients reported a higher proportion of blood and lymphatic disorders, while reports of nervous system and musculoskeletal/connective tissue disorders were more common in adults. The spectrum of AEs extracted from pharmacovigilance reports was similar to clinical trials. The JAKi AE profiles we observed may prove helpful in counseling patients and their parents before starting therapy and for monitoring once patients are on therapy.
Additional Info
Analysis of publicly available adverse events reported for pediatric patients treated with Janus kinase inhibitors
Pediatr Dermatol 2024 Sep 05;[EPub Ahead of Print], S Talasila, E Lee, EM Teichner, EC Siegfried, SR Jackson CullisonFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Janus kinase inhibitors (JAKi) are the new emerging immunomodulators in the dermatology world with a multitude of dermatologic and non-dermatologic indications encompassing adults and recently children. Being familiar with the efficacy and safety profile of these medications is of paramount importance for serving our patients with chronic skin diseases.
This review analysed the pharmacovigilance data extracted from the FDA's Adverse Event Reporting System and the Canada Vigilance Adverse Reaction Online Database between November 2011 and February 2023, for five JAKis, including: baricitinib, upadacitinib, abrocitinib, ruxolitinib, and tofacitinib. The reviewers analyzed 399,649 AEs from 133,216 adults and 2883 AEs from 955 patients under 18 years old. Both groups (adults and children) had increased risk of infections, constitutional symptoms and gastrointestinal symptoms. However, the pediatric population had an increase in reported hematologic and lymphatic disorders (neutropenia, thrombocytopenia and anemia); whereas, the adult population had an increase in musculoskeletal and nervous system disorders compared with children. The reviewers then stratify these adverse events per each drug. Ruxolitinib was associated with the most hematologic AEs in children. Tofacitinib mainly caused constitutional and musculoskeletal symptoms in children. Baricitinib was linked to gastrointestinal disorders including transaminitis and respiratory disorders in kids. Upadacitinib was associated with increased risk of infections and constitutional symptoms. In addition, upadacitinib had the highest risk for skin disorders, mainly acne, in children; whereas, baricitinib had no reported cutaneous AEs. Abrocitinib AEs in children were mainly hematologic disorders and increased risk of infections. The proportion of reported boxed-warning AEs (serious infection, mortality, malignancy, adverse cardiovascular events, and thrombosis) were overall lower for children compared with adults except for baricitinib where they were comparable. In conclusion, when used in children, it is advisable to monitor for blood disorders with ruxolitinib and abrocitinib, liver enzymes for baricitinib and musculoskeletal, and connective tissue disorders with tofacitinib and upadacitinib.
The study is limited by the retrospective nature and the risk of under-reporting or over-reporting and recall biases. In addition, the free database is constricted by sufficient objective evidence to be listed, so this might not be representing the full spectrum of AEs. Also, the approval for different JAKi was not granted simultaneously, so it is expected that the oldest approved JAKi will have the highest number of AEs reported, as is the case with ruxolitinib.
In summary, this review will help guide clinicians in counseling their patients on adverse events of JAKi in adults and children and in monitoring their laboratory data.